Leland Stanford Junior University

Nir Qvit

Daria D Mochly-Rosen

Xin Qi

Marie-Helene Disatnik Dziesietnik

Daria Mochly-rosen

The present disclosure provides peptides and constructs that inhibit mitochondrial fission, and compositions comprising the peptides or constructs. The present disclosure provides methods of reducing abnormal mitochondrial fission in a cell. Also provided are methods for designing and validating mitochondrial fission inhibitor constructs and peptides, including but not limited to, evaluating the effects of the constructs and peptides on binding of dynamin-1-related protein (Drp1) GTPase activity, Drp1 to mitochondrial fission 1 protein (Fis1), reduction of mitochondrial damage, reduction in cell death, inhibition of mitochondrial fragmentation in a cell under pathological conditions, and reduced loss of neurites in primary dopaminergic neurons in a Parkinsonism cell culture.

Inhibitors of mitochondrial fission and methods of use thereof

A peptide composition is provided which specifically inhibits the ability of &#x3b4;-protein kinase C (&#x3b4;PKC) to phosphorylate pyruvate dehydrogenase kinase (PDK) under ischemic conditions. The peptide composition is useful for treating or reducing tissue damage resulting from ischemia and/or reperfusion.

Compositions and methods for specific regulation of pyruvate dehydrogenase kinase

The present disclosure provides peptides and constructs that inhibit mitochondrial fission, and compositions comprising the peptides or constructs. The present disclosure provides methods of reducing abnormal mitochondrial fission in a cell. Also provided are methods for designing and validating mitochondrial fission inhibitor constructs and peptides, including but not limited to, evaluating the effects of the constructs and peptides on dynamin- 1-related protein (Drp1) GTPase activity, binding of Drp1 to mitochondrial fission 1 protein (Fis1), reduction of mitochondrial damage, reduction in cell death, inhibition of mitochondrial fragmentation in a cell under pathological conditions, and reduced loss of neurites in primary dopaminergic neurons in a Parkinsonism cell culture.

A peptide composition is provi'deo! which specifically inhibits the ability of &#x3b4; protein kinase C (&#x3b4;PKC) to phosphor/late pyruvate dehydrogenase kinase (PDK) under ischemic conditions. The peptide composition is useful for treating or reducing tissue damage resulting from ischemia and/or reperfusion.

The present disclosure provides peptides and constructs that inhibit mitochondrial fission, and compositions comprising the peptides or constructs. The present disclosure provides methods of reducing abnormal mitochondrial fission in a cell. Also provided are methods for designing and validating mitochondrial fission inhibitor constructs and peptides, including but not limited to, evaluating the effects of the constructs and peptides on dynamin 1-like protein (Drp1) guanosine triphosphate phosphatase (GTPase) activity, binding of Drp1 to mitochondrial fission 1 protein (Fis1), reduction of mitochondrial damage, reduction in cell death, inhibition of mitochondrial fragmentation in a cell under pathological conditions, and reduced loss of neurites in primary dopaminergic neurons in a Parkinsonism cell culture.

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Menlo Park, CA, United States of America

Nir Qvit